Gold-catalyzed stereoselective cycloisomerization of allenoic acids for two types of common natural γ-butyrolactones

Abstract

γ-(E)-Vinylic and γ-alkylic γ-butyrolactones are two different types of lactones existing extensively in animals and plants and many of them show interesting biological activities. Nature makes alkylic γ-butyrolactones by many different enzymatic lactonization processes. Scientists have been mimicking the natural strategy by developing new catalysts. However, direct and efficient access to γ-(E)-vinylic γ-butyrolactones is still extremely limited. Here, we wish to present our modular allene approach, which provides an efficient asymmetric approach to (E)-vinylic γ-butyrolactones from allenoic acids by identifying a new gold complex as the catalyst. Based on this cycloisomerization strategy, the first syntheses of racemic xestospongiene and xestospongienes E, F, G, and H have been realized and the absolute configurations of the chiral centers in xestospongienes E and F have been revised. In addition, by applying a C–O bond cleavage-free hydrogenation, the syntheses of naturally occurring γ-alkylic γ-lactones, (R)-4-tetradecalactone, (S)-4-tetradecalactone, (R)-γ-palmitolactone, and (R)-4-decalactone, have also been achieved.

Catalytic enantioselective construction of axial chirality in 1,3-disubstituted allenes

“…Readily available racemic allenyl carbonate 1l 49–51 reacted with malonate 2a under a set of similar reaction conditions at 25 °C with (±)-BINAP as the ligand to afford allene (±)- 3la in 83% yield, which underwent alkaline hydrolysis, HOAc-mediated decarboxylation, and further alkaline hydrolysis to afford 4-allenoic acid (±)- 4la in 78% yield. Then Au-catalyzed cycloisomerization of (±)- 4la was applied to generate γ-butyrolactone bearing a trans C=C bond (±)- 5la in 92% yield with 96:4 of E / Z selectivity 24 . After sequential hydrogenation of (±)- 5la and Fe-TEMPO-catalyzed aerobic oxidation 60,61 of the resulting hydrogenated product without purification, (±)-traumatic lactone was afforded in 79% yield.

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“…1,3-Disubstituted allenes with synthetically useful functionalities are of particular high interest due to their common existence in natural products/drug molecules (Fig. 1) 18 and their great potentials in the synthesis of natural products 19–24 . Thus, there is an urgent need for the development of catalytic highly enantioselective synthesis of such 1,3-disubstituted allenes.

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Efficient Syntheses of Traumatic Lactone and Rhizobialide

“…Recently, ATA (allenation of terminal alkynes) reactions have emerged as a powerful method to prepare functionalized allenes. On the other hand, we have developed the strategy that utilizes allenoic acid to construct the lactone ring by using Au catalysis to modulate the control of axial‐to‐central chirality transfer efficiency and Z / E selectivity; specifically, the stereoselective cyclization of allenoic acid . We envisage that combination of the ATA reaction with Au catalysis could be exploited for the synthesis of traumatic lactones.…”

“…ATA reaction of ethyl 4‐pentynoate 8 and aldehyde 6 in the presence of diphenylprinol afforded allenoate rac ‐ 9 , which was hydrolyzed to afford allenoic acid rac ‐ 10 . Its AuCl(LB‐Phos)‐catalyzed cyclization afforded E ‐alkenyl lactone ( E )‐ 11 with an E / Z selectivity of 96:4. The C=C bond and benzyl ether unit in this product were hydrogenated and cleaved simultaneously to afford lactone rac ‐ 12 with a terminal primary alcohol unit.…”

“…Typical procedure IV : To a dried Schlenk tube were added AgOTs (0.0171 g, 0.06 mmol, weighed in a glove box, 98 %), AuCl(LB‐Phos) (0.0358 g, 0.06 mmol), and CHCl 3 (6 mL) under a nitrogen atmosphere, sequentially. After stirring for 15 min, rac ‐ 10 (0.3616 g, 1.2 mmol) and CHCl 3 (6 mL) were added.…”